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1.
Transl Vis Sci Technol ; 13(9): 12, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39235401

RESUMEN

Purpose: To develop a novel classification of highly myopic eyes using artificial intelligence (AI) and investigate its relationship with contrast sensitivity function (CSF) and fundus features. Methods: We enrolled 616 highly myopic eyes of 616 patients. CSF was measured using the quantitative CSF method. Myopic macular degeneration (MMD) was graded according to the International META-PM Classification. Thickness of the macula and peripapillary retinal nerve fiber layer (p-RNFL) were assessed by fundus photography and optical coherence tomography, respectively. Classification was performed by combining CSF and fundus features with principal component analysis and k-means clustering. Results: With 83.35% total variance explained, highly myopic eyes were classified into four AI categories. The percentages of AI categories 1 to 4 were 14.9%, 37.5%, 36.2%, and 11.4%, respectively. Contrast acuity of the eyes in AI category 1 was the highest, which decreased by half in AI category 2. For AI categories 2 to 4, every increase in category led to a decrease of 0.23 logarithm of the minimum angle of resolution in contrast acuity. Compared with those in AI category 1, eyes in AI category 2 presented a higher percentage of MMD2 and thinner temporal p-RNFL. Eyes in AI categories 3 and 4 presented significantly higher percentage of MMD ≥ 3, thinner nasal macular thickness and p-RNFL (P < 0.05). Multivariate regression showed AI category 4 had higher MMD grades and thinner macular compared with AI category 3. Conclusions: We proposed an AI-based classification of highly myopic eyes with clear relevance to visual function and fundus features. Translational Relevance: This classification helps to discover the early hidden visual deficits of highly myopic patients, becoming a useful tool to evaluate the disease comprehensively.


Asunto(s)
Inteligencia Artificial , Sensibilidad de Contraste , Fondo de Ojo , Tomografía de Coherencia Óptica , Humanos , Femenino , Masculino , Persona de Mediana Edad , Tomografía de Coherencia Óptica/métodos , Anciano , Sensibilidad de Contraste/fisiología , Agudeza Visual/fisiología , Adulto , Miopía Degenerativa/fisiopatología , Miopía Degenerativa/diagnóstico por imagen , Miopía Degenerativa/diagnóstico , Miopía Degenerativa/clasificación , Miopía Degenerativa/patología , Degeneración Macular/clasificación , Degeneración Macular/fisiopatología , Degeneración Macular/diagnóstico , Degeneración Macular/patología , Degeneración Macular/diagnóstico por imagen , Mácula Lútea/patología , Mácula Lútea/diagnóstico por imagen , Mácula Lútea/fisiopatología , Fibras Nerviosas/patología
2.
Eye (Lond) ; 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39279010

RESUMEN

BACKGROUND: To investigate the morphologic features of iris in the highly myopic (HM) eyes using a novel swept-source optical coherence tomography (SS-OCT). METHODS: In this retrospective case-control study, 100 eyes of 100 patients scheduled to have cataract surgery were included, categorized into the control (22 mm< AL < 24.5 mm) and HM (AL ≥ 26 mm) groups. Iris volume (IV), area of anterior iris surface (IS), area of posterior IS, and average iris thickness (IT), as well as anterior chamber volume (ACV) and trabecular-iris space at 500 µm (TISA 500) were evaluated using SS-OCT. The associated factors with morphologic features of iris were also investigated. RESULTS: The HM group showed significantly larger IV and area of anterior and posterior IS than the control group (all P < 0.001), while no difference was identified in IT between the groups. Similar trend in IV was seen in the superior and nasal segments, and area of anterior and posterior IS showed similar trends in all segments except the temporal segment. The IV, area of anterior and posterior IS were all positively correlated with AL (all P < 0.001). Multivariate linear regression revealed that a larger IV was associated with greater ACV. Both larger areas of anterior IS and posterior IS were associated with male, longer AL, greater ACV, and smaller TISA 500. CONCLUSIONS: The HM eyes showed larger IV and area of IS than the control eyes, indicating a coronal expansion of the iris with AL. Iris morphology correlated with anterior chamber angle configuration.

3.
J Immunother Cancer ; 12(8)2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39174053

RESUMEN

BACKGROUND: Immune escape is an important feature of hepatocellular carcinoma (HCC). The overall response rate of immune checkpoint inhibitors (ICIs) in HCC is still limited. Revealing the immune regulation mechanisms and finding new immune targets are expected to further improve the efficacy of immunotherapy. Our study aims to use CRISPR screening mice models to identify potential targets that play a critical role in HCC immune evasion and further explore their value in improving immunotherapy. METHODS: We performed CRISPR screening in two mice models with different immune backgrounds (C57BL/6 and NPG mice) and identified the immunosuppressive gene Gsk3a as a candidate for further investigation. Flow cytometry was used to analyze the impact of Gsk3a on immune cell infiltration and T-cell function. RNA sequencing was used to identify the changes in neutrophil gene expression induced by Gsk3a and alterations in downstream molecules. The therapeutic value of the combination of Gsk3a inhibitors and anti-programmed cell death protein-1 (PD-1) antibody was also explored. RESULTS: Gsk3a, as an immune inhibitory target, significantly promoted tumor growth in immunocompetent mice rather than immune-deficient mice. Gsk3a inhibited cytotoxic T lymphocytes (CTLs) function by inducing neutrophil chemotaxis. Gsk3a promoted self-chemotaxis of neutrophil expression profiles and neutrophil extracellular traps (NETs) formation to block T-cell activity through leucine-rich α-2-glycoprotein 1 (LRG1). A significant synergistic effect was observed when Gsk3a inhibitor was in combination with anti-PD-1 antibody. CONCLUSIONS: We identified a potential HCC immune evasion target, Gsk3a, through CRISPR screening. Gsk3a induces neutrophil recruitment and NETs formation through the intermediate molecule LRG1, leading to the inhibition of CTLs function. Targeting Gsk3a can enhance CTLs function and improve the efficacy of ICIs.


Asunto(s)
Carcinoma Hepatocelular , Inmunoterapia , Neoplasias Hepáticas , Animales , Humanos , Ratones , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Línea Celular Tumoral , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3/metabolismo , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Evasión Inmune , Inmunoterapia/métodos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Ratones Endogámicos C57BL , Escape del Tumor/efectos de los fármacos
4.
Hum Vaccin Immunother ; 20(1): 2387461, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-39149877

RESUMEN

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory tissue disease. In view of the explosive growth in research on SLE, bibliometrics was performed to evaluate the 100 top-cited papers in this realm. We performed the search with terms "systemic lupus erythematosus" the Web of Science Core Collection database on May 3, 2023. Relevant literatures were screened. Data were extracted and analyzed by SPSS. The citations of 100 top-cited SLE studies spanned from 472 to 13,557. Most studies (60 out of 100) were conducted in the United States. Total citation times were positively associated with ACY, which was negatively correlated with the length of time since publication. Approximately half of the studies focused on the underlying mechanisms of SLE. New biologic therapies garnered attention and development. Our findings provide valuable insights into the developments in crucial areas of SLE and shed contributions to future studies.


Asunto(s)
Bibliometría , Lupus Eritematoso Sistémico , Humanos
5.
Heliyon ; 10(11): e32015, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38947456

RESUMEN

Background: Non-small cell lung Cancer (NSCLC) persists as a lethal neoplastic manifestation, exhibiting a diminished 5-year survival rate, partially attributable to chemotherapeutic resistance. This investigative endeavor aimed to elucidate the synergistic antineoplastic effects and underlying mechanisms of the SMYD2 inhibitor BAY-598 and the chemotherapeutic agent doxorubicin (DOX) in NSCLC. Methods: The human non-small cell lung cancer cell lines A549 and H460 were subjected to treatment regimens involving BAY-598 and/or DOX. Cellular viability, apoptotic events, invasive capacity, and migratory potential were evaluated through the implementation of CCK-8 assays, flow cytometric analyses, and Transwell assays, respectively. Protein expression levels were quantified via Western blot analyses. An in vivo xenograft murine model was established to assess therapeutic efficacy. Results: BAY-598 and DOX synergistically suppressed the viability, invasiveness, and migratory capabilities of NSCLC cells. Co-treatment Promoting cell apoptosis and cell cycle arrest. Additionally, Furthermore, co-administration significantly inhibited cell migration and invasion. Mechanistic studies revealed coordinately inhibited JAK-STAT signaling upon combination treatment. In vivo study further validated the synergistic antitumor efficacy of BAY-598 and DOX against NSCLC xenografts. Conclusions: Our findings demonstrate that BAY-598 potentiates the anti-cancer effects of DOX in non-small cell lung cancer cells by modulating the JAK/STAT signaling pathway as a synergistic strategy. The combination holds promise as an emerging therapeutic strategy for NSCLC. Further optimization and validation are warranted to promote its translational potential.

6.
Adv Ophthalmol Pract Res ; 4(3): 156-163, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39036706

RESUMEN

Background: High myopia is one of the major causes of visual impairment and has an ever-increasing prevalence, especially in East Asia. It is characterized by excessive axial elongation, leading to various blinding complications that extend beyond mere refractive errors and persist immovably after refractive surgery, presenting substantial public health challenge. Main text: High myopia-related complications include lens pathologies, atrophic and tractional maculopathy, choroidal neovascularization, peripheral retinal degenerations and retinal detachment, and glaucoma and heightened susceptibility to intraocular pressure (IOP) elevation. Pathological lens changes characteristic of high myopia include early cataractogenesis, overgrowth of lens, weakened zonules, and postoperative capsular contraction syndrome, possibly driven by inflammatory pathogenesis, etc. Dome-shaped macula and cilioretinal arteries are two newly identified protective factors for central vision of highly myopic patients. These patients also face risks of open-angle glaucoma and IOP spike following intraocular surgery. Morphologic alternations of optic nerve in high myopia can complicate early glaucoma detection, necessitating comprehensive examinations and close follow-up. Anatomically, thinner trabecular meshwork increases this risk; conversely lamina cribrosa defects may offer a fluid outlet, potentially mitigating the pressure. Notably, anxiety has emerged as the first recognized extra-ocular complication in high myopia, with an underlying inflammatory pathogenesis that connects visual stimulus, blood and brain. Conclusions: High myopia induces multiple ocular and potential mental health complications, underscoring the need to develop more effective strategies to improve both physical and emotional well-being of these patients, among which anti-inflammation might possibly represent a promising new target.

7.
Mol Cell Proteomics ; 23(6): 100783, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38729610

RESUMEN

High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia.


Asunto(s)
Autoanticuerpos , Autoinmunidad , Epitelio Pigmentado de la Retina , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/metabolismo , Masculino , Femenino , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Persona de Mediana Edad , Miopía Degenerativa/inmunología , Miopía/inmunología , Adulto
8.
Life Sci ; 347: 122650, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38631669

RESUMEN

AIMS: As a unique iron-dependent non-apoptotic cell death, Ferroptosis is involved in the pathogenesis and development of many human diseases and has become a research hotspot in recent years. However, the regulatory role of ferroptosis in the gut-liver-brain axis has not been elucidated. This paper summarizes the regulatory role of ferroptosis and provides theoretical basis for related research. MATERIALS AND METHODS: We searched PubMed, CNKI and Wed of Science databases on ferroptosis mediated gut-liver-brain axis diseases, summarized the regulatory role of ferroptosis on organ axis, and explained the adverse effects of related regulatory effects on various diseases. KEY FINDINGS: According to our summary, the main way in which ferroptosis mediates the gut-liver-brain axis is oxidative stress, and the key cross-talk of ferroptosis affecting signaling pathway network is Nrf2/HO-1. However, there were no specific marker between different organ axes mediate by ferroptosis. SIGNIFICANCE: Our study illustrates the main ways and key cross-talk of ferroptosis mediating the gut-liver-brain axis, providing a basis for future research.


Asunto(s)
Encéfalo , Ferroptosis , Hígado , Estrés Oxidativo , Ferroptosis/fisiología , Humanos , Estrés Oxidativo/fisiología , Encéfalo/metabolismo , Hígado/metabolismo , Hígado/patología , Animales , Eje Cerebro-Intestino/fisiología , Transducción de Señal , Factor 2 Relacionado con NF-E2/metabolismo
9.
Retina ; 44(5): 810-819, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38194664

RESUMEN

PURPOSE: To investigate the efficacy of combined application of B-scan ultrasonography (US) and ultrawide field imaging (UWFI) in detecting retinal tears before cataract surgery. METHODS: Of 1,277 cataract patients, 2,552 eyes were enrolled and received both B-scan US and UWFI examinations preoperatively. Three types of combination were applied: type 1 (union, B-scan US or centered UWFI), type 2 (intersection, B-scan US and centered UWFI), and type 3 (B-scan US and eye-steering UWFI). Sensitivity and specificity of detecting retinal tears by different methods were assessed. RESULTS: Totally 4.55% (116/2,552) of eyes were presented with retinal tears. The sensitivity of B-scan US and UWFI was 87.93% and 84.48%, and specificity was 95.16% and 99.79%, respectively. By applying type 1 and type 2 combination, the sensitivity was 98.28% and 74.14%, and specificity was 95.03% and 99.92%, respectively. By type 3 combination, the sensitivity increased to 95.69% and specificity to 99.88%, both of which were comparable to indirect ophthalmoscopy regardless of the number, type, and location of tears ( P > 0.05). In eyes with any cataract type or axial length, type 3 combination also gained comparable performance to indirect ophthalmoscopy. CONCLUSION: Combined application of B-scan US and eye-steering UWFI presented satisfactory performance in detecting retinal tears before cataract surgery.


Asunto(s)
Extracción de Catarata , Perforaciones de la Retina , Ultrasonografía , Humanos , Masculino , Femenino , Anciano , Perforaciones de la Retina/diagnóstico por imagen , Perforaciones de la Retina/diagnóstico , Ultrasonografía/métodos , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Catarata , Sensibilidad y Especificidad , Cuidados Preoperatorios/métodos , Estudios Retrospectivos , Reproducibilidad de los Resultados
10.
Artículo en Inglés | MEDLINE | ID: mdl-38292140

RESUMEN

Purpose: To investigate the value of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and ApoA1/B ratio in pathogenic diagnosis of chronic obstructive pulmonary disease (COPD) complicated by acute lower respiratory tract infection, assisting comprehensive disease assessment. Patients and Methods: The study enrolled 171 COPD patients with acute lower respiratory tract infections, 35 COPD patients without acute lower respiratory tract infections, and 41 healthy controls. Correlation analysis and binary logistic regression were used to assess the roles of various factors in COPD with acute lower respiratory tract infections. Receiver operating characteristic (ROC) curves were plotted and area under curves (AUC) values were calculated to evaluate the predictive performance. Results: Infections were the cause of alterations in ApoA1, ApoB and ApoA1/B index. In correlation analysis for pathogenic diagnosis of COPD complicated by acute lower respiratory infections, age, ApoA1, ApoA1/B ratio, lymphocyte count (LYMPH), neutrophil count (NEUT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and endotoxin were significantly correlated. For predicting COPD complicated by acute lower respiratory tract bacterial infection, ApoA1 had the highest area under the ROC curve (AUC: 0.889), with sensitivity and specificity of 82.9% and 83.9%, respectively. The combination of NEUT and ApoA1 improved the prediction efficacy (AUC: 0.909; sensitivity/specificity: 85.1%/85.7%). Conclusion: ApoA1, ApoB, and ApoA1/B ratio are good indicators for predicting pathogens in COPD complicated by acute lower respiratory tract infection, especially ApoA1 which has high predictive value.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Infecciones del Sistema Respiratorio , Humanos , Apolipoproteína A-I , Apolipoproteínas B , Biomarcadores , Estudios Transversales , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Infecciones del Sistema Respiratorio/diagnóstico
11.
Small ; 20(1): e2304491, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37653587

RESUMEN

A composite nanoagent capable of phototriggered tumor microenvironment (TME) regulation is developed based on copper (II) metal-organic frameworks (MOFs) with encapsulation of blebbistatin (Bb) and surface modification of fibroblast activation protein-αtargeted peptide (Tp). Tp enables active targeting of the nanoagents to cancer-associated fibroblast (CAF) while near-infrared light triggers Cu2+ -to-Cu+ photoreduction in MOFs, which brings about the collapse of MOFs and the release of Bb and Cu+ . Bb mediates photogeneration of hydroxyl radicals (•OH) and therefore inhibits extracellular matrix production by inducing CAF apoptosis, which facilitates the penetration of nanoagent to deep tumor tissue. The dual-channel generation of •OH based on Bb and the Cu+ species, via distinct mechanisms, synergistically reinforces oxidative stress in TME capable of inducing immunogenic cell death, which activates the antitumor immune response and therefore reverses the immunosuppressive TME. The synergistic antitumor phototherapy efficacy of such a type of nanoagent based on the abovementioned TME remodeling is unequivocally verified in a cell-derived tumor xenograft model.


Asunto(s)
Fibroblastos Asociados al Cáncer , Estructuras Metalorgánicas , Neoplasias , Humanos , Estructuras Metalorgánicas/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Microambiente Tumoral , Cobre/metabolismo , Neoplasias/metabolismo , Línea Celular Tumoral
12.
Front Med (Lausanne) ; 10: 1128818, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37795415

RESUMEN

Myopia is the leading cause of visual impairment in the world. With ever-increasing prevalence in these years, it creates an alarming global epidemic. In addition to the difficulty in seeing distant objects, myopia also increases the risk of cataract and advances its onset, greatly affecting the productivity of myopes of working age. Cataract management in myopic eyes, especially highly myopic eyes is originally more complicated than that in normal eyes, whereas the growing population of cataract with myopia, increasing popularity of corneal and lens based refractive surgery, and rising demand for spectacle independence after cataract surgery all further pose unprecedented challenges to ophthalmologists. Previous history of corneal refractive surgery and existence of implantable collamer lens will both affect the accuracy of biometry including measurement of corneal curvature and axial length before cataract surgery, which may result in larger intraocular lens (IOL) power prediction errors and a compromise in the surgical outcome especially in a refractive cataract surgery. A prudent choice of formula for cataract patients with different characteristics is essential in improving this condition. Besides, the characteristics of myopic eyes might affect the long-term stability of IOL, which is important for the maintenance of visual outcomes especially after the implantation of premium IOLs, thus a proper selection of IOL accordingly is crucial. In this mini-review, we provide an overview of the impact of myopia epidemic on treatment for cataract and to discuss new challenges that surgeons may encounter in the foreseeable future when planning refractive cataract surgery for myopic patients.

13.
Adv Mater ; 35(48): e2302503, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37681753

RESUMEN

Only a minority of rheumatoid arthritis (RA) patients achieve disease remission, so the exploration of additional pathogenic factors and the development of new therapeutics are needed. Here, strong correlations among the cell-free DNA (cfDNA) level and the inflammatory response in clinical synovial fluid samples and RA disease activity are discovered. The important role of cfDNA in disease development in a collagen-induced arthritis (CIA) murine model is also demonstrated. Building on these findings, a novel therapeutic based on anti-inflammatory (M2) macrophage-derived exosomes as chassis, that are modified with both oligolysine and matrix metalloproteinase (MMP)-cleavable polyethylene glycol (PEG) on the membrane, is developed. After intravenous injection, PEG-enabled prolonged circulation and C─C motif chemokine ligand-directed accumulation together result in enrichment at inflamed joints. Following subsequent MMP cleavage, the positively charged oligolysine is exposed for cfDNA scavenging, while exosomes induce M2 polarization. By using a classical CIA murine model and a newly established CIA canine model, it is demonstrated that the rationally designed exosome therapeutic substantially suppresses inflammation in joints and provides strong chondroprotection and osteoprotection, revealing its potential for effective CIA amelioration.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Exosomas , Humanos , Animales , Perros , Ratones , Modelos Animales de Enfermedad , Exosomas/patología , Artritis Reumatoide/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Inflamación/patología , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/inducido químicamente , Artritis Experimental/patología , Macrófagos/patología
14.
Cell Discov ; 9(1): 94, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37699875

RESUMEN

High myopia is a leading cause of blindness worldwide. It may lead to emotional defects that rely closely on the link between visual sensation and the central nervous system. However, the extent of the defects and its underlying mechanism remain unknown. Here, we report that highly myopic patients exhibit greater anxiety, accompanied by higher CC chemokine ligand 2 (CCL2) and monocyte levels in the blood. Similar findings are found in the mouse model of high myopia. Mechanistic evaluations using GFP-positive bone marrow chimeric mice, parabiotic mouse model, enhanced magnetic resonance imaging, etc., show that highly myopic visual stimulation increases CCL2 expression in eyes, aggravates monocyte/macrophage infiltration into eyes and brains, and disrupts blood-ocular barrier and blood-brain barrier of mice. Conversely, Ccl2-deficient highly myopic mice exhibit attenuated ocular and brain infiltration of monocytes/macrophages, reduced disruption of the blood-ocular barrier and blood-brain barrier, and less anxiety. Substantial alleviation of high myopia-related anxiety can also be achieved with the administration of CCL2-neutralizing antibodies. Our results establish the association between high myopia and anxiety, and implicate the CCL2-mediated inflammatory pathogenesis as an underlying mechanism.

15.
J Hazard Mater ; 460: 132365, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37639791

RESUMEN

For the purpose of searching for efficient photocatalysts to deal with recalcitrant organic micropollutants in wastewater, here an in-situ supramolecule self-assembly-thermal polymerization strategy is developed to prepare a series of porous cyclopentadiene (CPD) unit-incorporated g-C3N4 ultrathin nanosheets (CCPD-g-C3N4). The CCPD-g-C3N4 demonstrate CPD unit doping level-dependent and remarkably enhanced visible-light photocatalytic oxidation efficiency towards two organic micropollutants, acetaminophen and methylparaben, in which the optimized CCPD-g-C3N4-2 shows 6.1 and 3.5 times higher acetaminophen and methylparaben degradation rate than bulk g-C3N4; moreover, CCPD-g-C3N4-2 is still robust and efficient in the treatment of five mixed organic micropollutants in pharmaceutical wastewater, and the satisfactory micropollutant removal efficiency is obtained in a wide pH window and the presence of high concentrations of inorganic anions and cations as well as dissolved organic matters. Theoretical calculation combined with experimental test reveal that CCPD-g-C3N4 can significantly reduce ecological risk of the target pollutant after the photocatalytic degradation reaction. Such enhanced photocatalytic oxidation efficiency is dominated by the accelerated charge carrier separation dynamics and extended visible-light response region due to the incorporation of CPD units, which finally lead to the generation of abundant reactive oxygen species to degrade and mineralize target micropollutants efficiently.

16.
Nat Commun ; 14(1): 4505, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-37495590

RESUMEN

The therapeutic efficacy of whole tumor cell vaccines (TCVs) is modest, which has delayed their translation into personalized immunotherapies in the clinic. Here, we develop a TCV platform based on photothermal nanoparticle-loaded tumor cells, which can be rationally applied to diverse tumor types to achieve on-demand boost of anti-tumor immune responses for inhibiting tumor growth. During the fabrication process, mild photothermal heating by near-infrared (NIR) laser irradiation induces the nanoparticle-bearing tumor cells to express heat shock proteins as endogenous adjuvants. After a single vaccination at the back of tumor-bearing mice, non-invasive NIR laser irradiation further induces mild hyperthermia at vaccination site, which promotes the recruitment, activation, and antigen presentation by dendritic cells. Using an indicator we term fluctuation of tumor growth rate, we determine appropriate irradiation regimens (including optimized irradiation intervals and times). This TCV platform enables on-demand NIR manipulation of immune responses, and we demonstrate potent therapeutic efficacy against six murine models that mimick a range of clinical scenarios, including a model based on humanized mice and patient-derived tumor xenografts.


Asunto(s)
Hipertermia Inducida , Nanopartículas , Neoplasias , Vacunas , Humanos , Animales , Ratones , Línea Celular Tumoral , Fototerapia , Neoplasias/terapia , Presentación de Antígeno , Modelos Animales de Enfermedad , Rayos Láser
17.
Ophthalmol Ther ; 12(4): 2023-2033, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37178442

RESUMEN

INTRODUCTION: To evaluate the characteristics of optic nerve head (ONH) in highly myopic eyes and its role in predicting intraocular pressure (IOP) spikes after cataract surgery. METHODS: Patients who are highly myopic and were scheduled for cataract surgery were enrolled in this prospective case series study. IOP was measured preoperatively and at 1 day and 3 days postoperatively. ONH characteristics including area, tilt ratio, lamina cribrosa (LC) thickness, and depth, and the presence of LC defects were evaluated with enhanced depth imaging optical coherence tomography. Factors influencing LC defects and early IOP spike were investigated using multivariate stepwise logistic regression. RESULTS: In total, 200 highly myopic eyes of 200 patients were analyzed: 35.00% had small ONH, 53.00% had ONH tilt, and 14.00% had LC defects. Multivariate analysis demonstrated female patients with larger ONH area and deeper LC tended to have LC defects (all P < 0.05). As to postoperative IOP, IOP change, and incidence of IOP spikes, eyes with small ONH, ONH tilt, and LC defects had similar (all P > 0.05), higher (all P < 0.05), and lower (all P < 0.05) outcomes compared with those without the corresponding characteristic, respectively. Multivariate analysis showed that presence of LC defects and thicker LC were protective factors for early IOP spikes, and axial length > 28 mm was a risk factor (all P < 0.05). CONCLUSION: Female patients with larger ONH area and deeper LC tend to have LC defects, which, together with thicker LC, was correlated with less IOP spikes in highly myopic eyes. TRIAL REGISTRATION: This study was conducted as part of a larger project, the Shanghai High Myopia Study, registered at www. CLINICALTRIALS: gov (accession number NCT03062085).

18.
Biomed Pharmacother ; 162: 114672, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37060662

RESUMEN

In recent years, breakthroughs in bioinformatics have been made with the discovery of many functionally significant non-coding RNAs (ncRNAs). The discovery of these ncRNAs has further demonstrated the multi-level characteristics of intracellular gene expression regulation, which plays an important role in assisting diagnosis, guiding clinical drug use and determining prognosis in the treatment process of various diseases. microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are the three major types of ncRNAs that interact with each other. Studies have shown that lncRNAs and circRNAs can sponge miRNAs, thereby influencing normal physiological processes and regulating mRNA expression and, thus, the physiological state of cells. This paper summarizes the mechanism of action and research progress of the three ncRNA and seven types of modalities. This summary is intended to provide new ideas for diagnosing and treating diseases and researching and developing new drugs.


Asunto(s)
MicroARNs , ARN Largo no Codificante , MicroARNs/genética , ARN Circular/genética , ARN Largo no Codificante/genética , Regulación de la Expresión Génica , Biología Computacional
19.
Eye Vis (Lond) ; 10(1): 19, 2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37020245

RESUMEN

BACKGROUND: To investigate the visual and patient-reported outcomes of a diffractive trifocal intraocular lens (IOL) in highly myopic eyes. METHODS: Patients with planned cataract removal by phacoemulsification and implantation of a trifocal IOL (AT LISA tri 839MP) were enrolled in the prospective, multicenter cohort study. Patients were allocated into three groups according to their axial length (AL): control group, AL < 26 mm; high myopia group, AL 26-28 mm; extreme myopia group, AL ≥ 28 mm. At 3 months post-surgery, data for 456 eyes of 456 patients were collected, including visual acuity, defocus curve, contrast sensitivity (CS), visual quality, spectacle independence, and overall satisfaction. RESULTS: After surgery, the uncorrected distance visual acuity improved from 0.59 ± 0.41 to 0.06 ± 0.12 logMAR (P < 0.001). In all three groups, about 60% of eyes achieved uncorrected near and intermediate visual acuity of 0.10 logMAR or better, but significantly fewer eyes in the extreme myopia group achieved uncorrected distance visual acuity of 0.10 logMAR or better (P < 0.05). Defocus curves revealed that the visual acuity was significantly worse in the extreme myopia group than others at 0.00, - 0.50, and - 2.00 diopters (P < 0.05). CS did not differ between the control and high myopia groups but was significantly lower in the extreme myopia group at 3 cycles per degree. The extreme myopia group also had greater higher-order aberrations and coma, lower modulation transfer functions and VF-14 scores, more glare and halos, worse spectacle independence at far distance, and consequently lower patient satisfaction than others (all P < 0.05). CONCLUSIONS: In eyes with a high degree of myopia (AL < 28 mm), trifocal IOLs have been shown to provide similar visual outcomes to those in non-myopic eyes. However, in extremely myopic eyes, acceptable results may be obtained with trifocal IOLs, but a reduced level of uncorrected distance vision is expected.

20.
J Pers Med ; 13(3)2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36983583

RESUMEN

The outcomes of toric intraocular lens (IOL) implantation in correcting asymmetric bowtie corneal astigmatism remain uncertain. The accurate measurement of corneal astigmatism is essential for surgical planning. In this prospective cohort study, patients with asymmetric or symmetric bowtie corneal astigmatism who underwent toric IOL implantation were recruited. Preoperative corneal astigmatism was measured with an IOLMaster and Pentacam (including the simulated keratometry (SimK), total corneal refractive power (TCRP), and wavefront aberration (WFA) modes). At 3 months after surgery, the refractive outcomes and residual astigmatic refractive errors were compared with patients with symmetric bowtie astigmatism. The prediction errors (the differences between the calculated actual corneal astigmatism and the measured corneal astigmatism) were compared among the different measurement modes in the asymmetric group. There were no differences in residual astigmatism between the asymmetric and symmetric groups. However, the mean absolute residual astigmatic refractive error was greater in the asymmetric group than in the symmetric group (0.72 ± 0.42 D vs. 0.53 ± 0.24 D, p = 0.043). In the asymmetric group, the mean absolute prediction errors for the IOLMaster, SimK, TCRP and WFA modes were 0.53 ± 0.40, 0.56 ± 0.47, 0.68 ± 0.52, and 0.43 ± 0.40 D, respectively. The Pentacam WFA mode was the most accurate mode (p < 0.05). The absolute prediction error of the WFA mode was positively correlated with the total corneal irregular astigmatism higher-order aberrations and coma (r = 0.416 and r = 0.473, respectively; both p < 0.05). Our study suggests toric IOL implantation effectively corrected asymmetric bowtie corneal astigmatism. The Pentacam WFA mode may be the most accurate measurement mode, although its accuracy decreased as asymmetry increased.

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